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J Biol Chem, Vol. 275, Issue 11, 8032-8037, March 17, 2000
From Immunex Corporation, Seattle, Washington 98101
Crystals seldom form spontaneously within tissues
of mammals, except in the urinary tract or in association with
eosinophil-rich diseases in humans (Charcot-Leyden crystals).
Endogenously formed eosinophilic crystals have been reported in
respiratory tract and other tissues of several strains of mice, but the
biochemical characterization of these crystals has not been reported.
In this study, eosinophilic crystal formation was examined in
homozygous C57BL/6J viable motheaten mice, lung-specific surfactant
apoprotein C promoter/soluble human tumor necrosis factor p75 receptor
type II fusion protein transgenic mice (C57BL/6NTac × Sv/129),
and CD40L-deficient mice with spontaneous Pneumocystis
carinii infection. In viable motheaten but not wild type mice,
rapidly developing crystals represented a major feature of the fatal
lung injury induced by macrophage dysregulation. Conversely,
eosinophilic crystals did not form until 4-8 months of age in
transgenic and CD40L-deficient mice and were present in 10-30% of
age-matched wild type controls. Mass spectrometry analysis of proteins
from bronchoalveolar lavage fluid identified the crystals as Ym1,
sometimes referred to as T-lymphocyte-derived eosinophil chemotactic
factor. The Ym1 sequence was homologous to chitinase, and enzymatic
assays indicated a 3-5-fold increase in chitinase activity compared
with control mice. Intracellular and extracellular crystals associated with epithelial damage suggested that the crystals may contribute to
lung inflammation through mechanical damage and enzymatic degradation.
Biochemical Characterization of Endogenously Formed Eosinophilic
Crystals in the Lungs of Mice*
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom all correspondence should be addressed: Immunex Corp., 51 University St., Seattle, WA 98101. Tel.: 206-389-4361; Fax: 206-233-9733; E-mail: schuhj@immunex.com.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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